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Helicobacter pylori Regulates the Apoptosis of Human Megakaryocyte Cells via NF-κB/IL-17 Signaling

OBJECTIVE: To investigate the role of Helicobacter pylori (HP) on the regulation of NF-κB/IL-17 signaling, mechanisms underlying apoptosis in human megakaryocyte cell lines Dami. METHODS: Firstly, the mouse model of immune thrombocytopenia (ITP) was established. Then, the mice were subjected to gast...

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Autores principales: Lei, Huyi, Ma, Yongyong, Tan, Jie, Liu, Qifa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989681/
https://www.ncbi.nlm.nih.gov/pubmed/33776453
http://dx.doi.org/10.2147/OTT.S268056
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author Lei, Huyi
Ma, Yongyong
Tan, Jie
Liu, Qifa
author_facet Lei, Huyi
Ma, Yongyong
Tan, Jie
Liu, Qifa
author_sort Lei, Huyi
collection PubMed
description OBJECTIVE: To investigate the role of Helicobacter pylori (HP) on the regulation of NF-κB/IL-17 signaling, mechanisms underlying apoptosis in human megakaryocyte cell lines Dami. METHODS: Firstly, the mouse model of immune thrombocytopenia (ITP) was established. Then, the mice were subjected to gastric perfusion with HP. Next, the changes in platelet and bone marrow megakaryocyte classification were assessed in each group. Human megakaryocyte Dami cells were treated with HP in vitro for 3, 6, or 9 h; and the rates of apoptosis in each group were then evaluated with flow cytometry. Fluorescent quantitative PCR and Western blotting were implemented for assessing the expression of Bcl-2 and Bax, which are related to apoptosis, and p65, which is associated with the NF-κB pathway. The expression of these proteins was also evaluated after treatment with PDTC, an inhibitor of the NF-κB pathway inhibitor. RESULTS: In vivo, exogenous administration of HP was found to increase the optical density value for the anti-HP antibody in HP-infected BALB/c mice. Meanwhile, the platelet counts in the HP-infected ITP mice model were significantly reduced compared with non-infected ITP mice. In vitro, the apoptotic rate of Dami cells increased gradually with the prolongation of the exposure to HP; the most noticeable change was at 6 h, and there was a significant difference between 0 h and 6 h. The expression of Bax, p-p65, and IL-17 also increased progressively with the prolongation HP exposure, while the expression of anti-apoptotic Bcl-2 protein decreased gradually, especially at 6 h, and the expression of total p65 did not change significantly compared with baseline. Anecdotally, these effects were reversed by the application of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB signaling. CONCLUSION: HP can promote platelet destruction in ITP mice, and the underlying mechanisms may be related to accelerating apoptosis of megakaryocytes by the activation of the NF-κB/IL-17 pathway.
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spelling pubmed-79896812021-03-25 Helicobacter pylori Regulates the Apoptosis of Human Megakaryocyte Cells via NF-κB/IL-17 Signaling Lei, Huyi Ma, Yongyong Tan, Jie Liu, Qifa Onco Targets Ther Original Research OBJECTIVE: To investigate the role of Helicobacter pylori (HP) on the regulation of NF-κB/IL-17 signaling, mechanisms underlying apoptosis in human megakaryocyte cell lines Dami. METHODS: Firstly, the mouse model of immune thrombocytopenia (ITP) was established. Then, the mice were subjected to gastric perfusion with HP. Next, the changes in platelet and bone marrow megakaryocyte classification were assessed in each group. Human megakaryocyte Dami cells were treated with HP in vitro for 3, 6, or 9 h; and the rates of apoptosis in each group were then evaluated with flow cytometry. Fluorescent quantitative PCR and Western blotting were implemented for assessing the expression of Bcl-2 and Bax, which are related to apoptosis, and p65, which is associated with the NF-κB pathway. The expression of these proteins was also evaluated after treatment with PDTC, an inhibitor of the NF-κB pathway inhibitor. RESULTS: In vivo, exogenous administration of HP was found to increase the optical density value for the anti-HP antibody in HP-infected BALB/c mice. Meanwhile, the platelet counts in the HP-infected ITP mice model were significantly reduced compared with non-infected ITP mice. In vitro, the apoptotic rate of Dami cells increased gradually with the prolongation of the exposure to HP; the most noticeable change was at 6 h, and there was a significant difference between 0 h and 6 h. The expression of Bax, p-p65, and IL-17 also increased progressively with the prolongation HP exposure, while the expression of anti-apoptotic Bcl-2 protein decreased gradually, especially at 6 h, and the expression of total p65 did not change significantly compared with baseline. Anecdotally, these effects were reversed by the application of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB signaling. CONCLUSION: HP can promote platelet destruction in ITP mice, and the underlying mechanisms may be related to accelerating apoptosis of megakaryocytes by the activation of the NF-κB/IL-17 pathway. Dove 2021-03-19 /pmc/articles/PMC7989681/ /pubmed/33776453 http://dx.doi.org/10.2147/OTT.S268056 Text en © 2021 Lei et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Lei, Huyi
Ma, Yongyong
Tan, Jie
Liu, Qifa
Helicobacter pylori Regulates the Apoptosis of Human Megakaryocyte Cells via NF-κB/IL-17 Signaling
title Helicobacter pylori Regulates the Apoptosis of Human Megakaryocyte Cells via NF-κB/IL-17 Signaling
title_full Helicobacter pylori Regulates the Apoptosis of Human Megakaryocyte Cells via NF-κB/IL-17 Signaling
title_fullStr Helicobacter pylori Regulates the Apoptosis of Human Megakaryocyte Cells via NF-κB/IL-17 Signaling
title_full_unstemmed Helicobacter pylori Regulates the Apoptosis of Human Megakaryocyte Cells via NF-κB/IL-17 Signaling
title_short Helicobacter pylori Regulates the Apoptosis of Human Megakaryocyte Cells via NF-κB/IL-17 Signaling
title_sort helicobacter pylori regulates the apoptosis of human megakaryocyte cells via nf-κb/il-17 signaling
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989681/
https://www.ncbi.nlm.nih.gov/pubmed/33776453
http://dx.doi.org/10.2147/OTT.S268056
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